This study is designed to yield new information on the regulatory mechanisms that normally maintain self tolerance, using murine and avian models. Autoimmune thyroiditis can be induced in the genetically susceptible high responder mouse by injections of thyroglobulin (Tg), and occurs spontaneously in OS chickens. Both animal diseases resemble Hashimoto's disease in the presence of autoantibodies to Tg and mononuclear infiltration of the thyroid. Several hypotheses have been put forth to explain the maintenance of self tolerance to thyroid antigens: a) clonal deletion of self-reactive lymphocytes, b) parital clonal deletion (elimination of self-reactive T cells but not B cells) and c) active suppression. Recent findings from our laboratory strongly suggest the presence of self-reactive T cells and active suppression involved in regulation. This proposal is designed to test the above hypotheses by: 1) isolating and characterizing thyroid-specific autoreactive T cells, and 2) determining the role of thyroid gland activity, altered by hormonal means, in regulating the thyroid specific autoreactive T cells. Information obtained from these studies should help use to understand and perhaps prevent human autoimmune thyroid diseases.